PSE1 Activators

The class of chemicals identified as PSE1 activators comprises a diverse array of compounds, primarily characterized by their ability to influence the nuclear transport machinery. These compounds may not directly activate PSE1 but instead act on the broader regulatory network that PSE1 is a part of, which includes the intricate balance of nuclear import and export. For instance, compounds like Importazole and its analogs inhibit the function of importin-β, a key transporter that PSE1 interacts with, potentially leading to an upregulation of PSE1 activity to counterbalance the impaired transport mechanism. Similarly, molecules like Ivermectin disturb the protein transport across the nuclear membrane which may lead to a cellular response that enhances PSE1's role in the nuclear transport pathway.

On the other hand, some activators work by influencing the components and energy sources of the Ran gradient, a critical determinant of nuclear import. Compounds like RanBP1, RanGTP, and non-hydrolyzable GTP analogs modulate the Ran cycle's activity, subsequently affecting PSE1 indirectly. Moreover, energy-modulating agents like Bis (2,4,6-trichlorophenyl) oxalate could have an impact on PSE1 by altering the energetic milieu in which nuclear transport occurs.